tbuckley/cabot-search huggingface dataset:
Recurrent pancreatitis caused by previous coiling of a pancreaticoduodenal artery aneurysm in a patient with median arcuate ligament syndrome
Authors: Haruka Hagiwara, Ko Tomishima, Yasuhisa Jimbo, Mako Ushio, Akinori Suzuki, Toshio Fujisawa, Hiroyuki Isayama
Journal: Endoscopy (2023)

Median arcuate ligament syndrome (MALS), reported by Harjola in 1963 [1], involves a celiac artery stricture caused by compression of the ligament, resulting in reduction of blood perfusion to the abdominal organs. Rupture of a pancreaticoduodenal artery aneurysm has a high mortality rate of 14.3 %, even when treated with emergent transcatheter coil embolization [2]. We report a case of recurrent pancreatitis caused by main pancreatic duct (MPD) obstruction by a perforated coil after transcatheter embolization of a pancreaticoduodenal artery aneurysm caused by MALS.
A novel method, gel immersion endoscopic injection sclerotherapy, may make the procedure easier and more accurate
Authors: Noriaki Sugawara, Taro Iwatsubo, Hironori Tanaka, Akitoshi Hakoda, Kazuhiro Ota, Toshihisa Takeuchi, Hiroki Nishikawa
Journal: Endoscopy (2023)

Esophageal varices are caused by portal hypertension such as cirrhosis. Ruptured esophageal varices cause massive bleeding; therefore, preventive hemostasis is important. The standard procedures to prevent bleeding include endoscopic variceal ligation (EVL) and endoscopic injection sclerotherapy (EIS). EIS is a more difficult procedure than EVL but results in a lower recurrence rate and is more curative. In particular, problems are often faced in the process of inserting a needle into esophageal varices and injecting sclerosing agents into the vessel. Gel immersion endoscopy is a useful method for securing a visual field [1]. Additionally, a lower level of intraluminal pressure and wall tension is maintained [2] and the vessel lumen is kept thicker and wider than that during gas emersion ([Fig. 1]). Therefore, EIS with a "Viscoclear" gel (Otsuka Pharmaceutical Factory, Tokushima, Japan) may allow easier needle insertion and sclerosing material injection into esophageal varices.
A tent-like sign during endoscopic ultrasound-guided gastroenterostomy: an indication of a misdeployed stent in the peritoneum
Authors: Yu-Ting Kuo, Hsiu-Po Wang
Journal: Endoscopy (2023)

Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) with the use of a lumen-apposing metal stent (LAMS) is an established alternative technique for patients with malignant gastric outlet obstruction [1]. Although single-step delivery systems for LAMSs significantly reduce the risk of adverse events (AEs), stent misdeployment during EUS-GE remains the most common cause for technical failure and AEs. This report describes the case of a patient who underwent EUS-GE with deployment of the distal flange of the LAMS occurring in the peritoneum (type 1 stent misdeployment) [2].
Radical Cystectomy in the Treatment of Invasive Bladder Cancer: Long-Term Results in 1,054 Patients
Authors: John P. Stein, Gary Lieskovsky, Richard Cote, Susan Groshen, An-Chen Feng, Stuart Boyd, Eila Skinner, Bernard Bochner, Duriayai Thangathurai, Maged Mikhail, Derek Raghavan, DonaldG. Skinner
Journal: Journal of Clinical Oncology (2023)

To evaluate our long-term experience with patients treated uniformly with radical cystectomy and pelvic lymph node dissection for invasive bladder cancer and to describe the association of the primary bladder tumor stage and regional lymph node status with clinical outcomes.
Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms. Part II diagnosis and management
Authors: Brian M. Wei, Lindy P. Fox, Benjamin H. Kaffenberger, Abraham M. Korman, Robert G. Micheletti, Arash Mostaghimi, Megan H. Noe, Misha Rosenbach, Kanade Shinkai, Jason H. Kwah, Elizabeth J. Phillips, Jean L. Bolognia, William Damsky, Caroline A. Nelson
Journal: Journal of the American Academy of Dermatology (2023)
Micro-nanofiber composite biomimetic conduits promote long-gap peripheral nerve regeneration in canine models
Authors: Xianhao Dong, Yueyue Yang, Zheheng Bao, Adam C. Midgley, Feiyi Li, Shuxin Dai, Zhuangzhuang Yang, Jin Wang, Lihua Liu, Wenlei Li, Yayuan Zheng, Siyang Liu, Yang Liu, Weijian Yu, Jun Liu, Meng Fan, Meifeng Zhu, Zhongyang Shen, Gu Xiaosong, Deling Kong
Journal: Bioactive Materials (2023)

Peripheral nerve injuries may result in severe long-gap interruptions that are challenging to repair. Autografting is the gold standard surgical approach for repairing long-gap nerve injuries but can result in prominent donor-site complications. Instead, imitating the native neural microarchitecture using synthetic conduits is expected to offer an alternative strategy for improving nerve regeneration. Here, we designed nerve conduits composed of high-resolution anisotropic microfiber grid-cordes with randomly organized nanofiber sheaths to interrogate the positive effects of these biomimetic structures on peripheral nerve regeneration. Anisotropic microfiber-grids demonstrated the capacity to directionally guide Schwann cells and neurites. Nanofiber sheaths conveyed adequate elasticity and permeability, whilst exhibiting a barrier function against the infiltration of fibroblasts. We then used the composite nerve conduits bridge 30-mm long sciatic nerve defects in canine models. At 12 months post-implant, the morphometric and histological recovery, gait recovery, electrophysiological function, and degree of muscle atrophy were assessed. The newly regenerated nerve tissue that formed within the composite nerve conduits showed restored neurological functions that were superior compared to sheaths-only scaffolds and Neurolac nerve conduit controls. Our findings demonstrate the feasibility of using synthetic biophysical cues to effectively bridge long-gap peripheral nerve injuries and indicates the promising clinical application prospects of biomimetic composite nerve conduits.
Insights from linking police domestic abuse data and health data in South Wales, UK: a linked routine data analysis using decision tree classification
Authors: Natasha Kennedy, Tint Lwin Win, Amrita Bandyopadhyay, Jonathan Kennedy, Benjamin Rowe, Cynthia McNerney, Julie Evans, Karen Hughes, Mark A Bellis, Angela Jones, Karen Harrington, Simon Moore, Sinead Brophy
Journal: The Lancet Public Health (2023)

Exposure to domestic abuse can lead to long-term negative impacts on the victim's physical and psychological wellbeing. The 1998 Crime and Disorder Act requires agencies to collaborate on crime reduction strategies, including data sharing. Although data sharing is feasible for individuals, rarely are whole-agency data linked. This study aimed to examine the knowledge obtained by integrating information from police and health-care datasets through data linkage and analyse associated risk factor clusters.
Targeting leucine-rich repeat serine/threonine-protein kinase 2 sensitizes pancreatic ductal adenocarcinoma to anti-PD-L1 immunotherapy
Authors: Kang Sun, Xiaozhen Zhang, Mengyi Lao, Lihong He, Sicheng Wang, Hanshen Yang, Jian Xu, Jianghui Tang, Zhengtao Hong, Jinyuan Song, Chengxiang Guo, Muchun Li, Xinyuan Liu, Yan Chen, Hanjia Zhang, Jingxing Zhou, Jieru Lin, Sirui Zhang, Yifan Hong, Jinyan Huang, Tingbo Liang, Xueli Bai
Journal: Molecular Therapy (2023)

Pancreatic ductal adenocarcinoma (PDAC) is not sensitive to immune checkpoint blockade therapy, and negative feedback of tumor immune evasion might be partly responsible. We isolated CD8+ T cells and cultured them in vitro. Proteomics analysis was performed to compare changes in Panc02 cell lines cultured with conditioned medium, and leucine-rich repeat kinase 2 (LRRK2) was identified as a differential gene. LRRK2 expression was related to CD8+ T cell spatial distribution in PDAC clinical samples and upregulated by CD8+ T cells via interferon gamma (IFN-γ) simulation in vitro. Knockdown or pharmacological inhibition of LRRK2 activated an anti-pancreatic cancer immune response in mice, which meant that LRRK2 acted as an immunosuppressive gene. Mechanistically, LRRK2 phosphorylated PD-L1 at T210 to inhibit its ubiquitination-mediated proteasomal degradation. LRRK2 inhibition attenuated PD-1/PD-L1 blockade-mediated, T cell-induced upregulation of LRRK2/PD-L1, thus sensitizing the mice to anti-PD-L1 therapy. In addition, adenosylcobalamin, the activated form of vitamin B12, which was found to be a broad-spectrum inhibitor of LRRK2, could inhibit LRRK2 in vivo and sensitize PDAC to immunotherapy as well, which potentially endows LRRK2 inhibition with clinical translational value. Therefore, PD-L1 blockade combined with LRRK2 inhibition could be a novel therapy strategy for PDAC.
Ten years of treatment with ruxolitinib for myelofibrosis: a review of safety
Authors: Srdan Verstovsek, Ruben A. Mesa, Robert A. Livingston, Wilson Hu, John Mascarenhas
Journal: Journal of Hematology & Oncology (2023)

Abstract Myelofibrosis (MF) is a chronic myeloproliferative neoplasm characterized by bone marrow fibrosis, anemia, extramedullary hematopoiesis, and splenomegaly. Patients with MF are at risk for reduced survival versus the general population and often experience burdensome signs and symptoms that reduce quality of life. The oral Janus kinase (JAK) 1/JAK2 inhibitor ruxolitinib was initially approved by the US Food and Drug Administration in 2011 for the treatment of patients with intermediate or high-risk MF, including primary MF, post-polycythemia vera MF, and post-essential thrombocythemia MF, based on efficacy and safety findings from the randomized, controlled, phase 3 COMFORT trials. Over a decade later, ruxolitinib continues to be the standard of care in higher-risk MF, and dose optimization and management remain crucial for safely maximizing clinical benefits of ruxolitinib. This review summarizes the safety profile of ruxolitinib in patients with MF in the COMFORT trials leading up to approval and in the subsequent JUMP, ROBUST, EXPAND, and REALISE trials; in pooled analyses; and in postmarketing analyses in the 10 years following approval. There is a focus on the occurrence of common hematologic and nonhematologic adverse events, with guidance provided on the management of patients with anemia or thrombocytopenia, including dosing strategies based on findings from the REALISE and EXPAND trials. Finally, to ensure a greater understanding of the safety profile of ruxolitinib, practical considerations are discussed.
Olfactory chemosensation extends lifespan through TGF-β signaling and UPR activation
Authors: Evandro A. De-Souza, Maximillian A. Thompson, Rebecca C. Taylor
Journal: Nature Aging (2023)

Abstract Animals rely on chemosensory cues to survive in pathogen-rich environments. In Caenorhabditis elegans , pathogenic bacteria trigger aversive behaviors through neuronal perception and activate molecular defenses throughout the animal. This suggests that neurons can coordinate the activation of organism-wide defensive responses upon pathogen perception. In this study, we found that exposure to volatile pathogen-associated compounds induces activation of the endoplasmic reticulum unfolded protein response (UPR ER ) in peripheral tissues after xbp-1 splicing in neurons. This odorant-induced UPR ER activation is dependent upon DAF-7/transforming growth factor beta (TGF-β) signaling and leads to extended lifespan and enhanced clearance of toxic proteins. Notably, rescue of the DAF-1 TGF-β receptor in RIM/RIC interneurons is sufficient to significantly recover UPR ER activation upon 1-undecene exposure. Our data suggest that the cell non-autonomous UPR ER rewires organismal proteostasis in response to pathogen detection, pre-empting proteotoxic stress. Thus, chemosensation of particular odors may be a route to manipulation of stress responses and longevity.
An artificial intelligence-assisted physiologically-based pharmacokinetic model to predict nanoparticle delivery to tumors in mice
Authors: Wei-Chun Chou, Qiran Chen, Long Yuan, Yi-Hsien Cheng, Chunla He, Nancy A. Monteiro-Riviere, Jim E. Riviere, Zhoumeng Lin
Journal: Journal of Controlled Release (2023)

The critical barrier for clinical translation of cancer nanomedicine stems from the inefficient delivery of nanoparticles (NPs) to target solid tumors. Rapid growth of computational power, new machine learning and artificial intelligence (AI) approaches provide new tools to address this challenge. In this study, we established an AI-assisted physiologically based pharmacokinetic (PBPK) model by integrating an AI-based quantitative structure-activity relationship (QSAR) model with a PBPK model to simulate tumor-targeted delivery efficiency (DE) and biodistribution of various NPs. The AI-based QSAR model was developed using machine learning and deep neural network algorithms that were trained with datasets from a published "Nano-Tumor Database" to predict critical input parameters of the PBPK model. The PBPK model with optimized NP cellular uptake kinetic parameters was used to predict the maximum delivery efficiency (DEmax) and DE at 24 (DE24) and 168 h (DE168) of different NPs in the tumor after intravenous injection and achieved a determination coefficient of R2 = 0.83 [root mean squared error (RMSE) = 3.01] for DE24, R2 = 0.56 (RMSE = 2.27) for DE168, and R2 = 0.82 (RMSE = 3.51) for DEmax. The AI-PBPK model predictions correlated well with available experimentally-measured pharmacokinetic profiles of different NPs in tumors after intravenous injection (R2 ≥ 0.70 for 133 out of 288 datasets). This AI-based PBPK model provides an efficient screening tool to rapidly predict delivery efficiency of a NP based on its physicochemical properties without relying on an animal training dataset.
Itaconate inhibits CD103+ TRM cells and alleviates hepatobiliary injury in mouse models of primary sclerosing cholangitis
Authors: Yikang Li, Bo Li, Xiao Xiao, Qiwei Qian, Rui Wang, Zhuwan Lyu, Ruiling Chen, Nana Cui, Yiyan Ou, Xiting Pu, Qi Miao, Qixia Wang, Min Lian, M. Eric Gershwin, Ruqi Tang, Xiong Ma, Zhengrui You
Journal: Hepatology (2023)

Background and Aims: Primary sclerosing cholangitis (PSC) is a chronic progressive liver disease characterized by the infiltration of intrahepatic tissue-resident memory CD8 + T cells (T RM ). Itaconate has demonstrated therapeutic potential in modulating inflammation. An unmet need for PSC is the reduction of biliary inflammation, and we hypothesized that itaconate may directly modulate pathogenic T RM . Approach and Results: The numbers of intrahepatic CD103 + T RM were evaluated by immunofluorescence in PSC (n = 32), and the serum levels of itaconate in PSC (n = 64), primary biliary cholangitis (PBC) (n = 60), autoimmune hepatitis (AIH) (n = 49), and healthy controls (n = 109) were determined by LC-MS/MS. In addition, the frequencies and immunophenotypes of intrahepatic T RM using explants from PSC (n = 5) and healthy donors (n = 6) were quantitated by flow cytometry. The immunomodulatory properties of 4-octyl itaconate (4-OI, a cell-permeable itaconate derivative) on CD103 + T RM were studied in vitro. Finally, the therapeutic potential of itaconate was studied by the administration of 4-OI and deficiency of immune-responsive gene 1 (encodes the aconitate decarboxylase producing itaconate) in murine models of PSC. Intrahepatic CD103 + T RM was significantly expanded in PSC and was positively correlated with disease severity. Serum itaconate levels decreased in PSC. Importantly, 4-OI inhibited the induction and effector functions of CD103 + T RM in vitro. Mechanistically, 4-OI blocked DNA demethylation of RUNX3 in CD8 + T cells. Moreover, 4-OI reduced intrahepatic CD103 + T RM and ameliorated liver injury in murine models of PSC. Conclusions: Itaconate exerted immunomodulatory activity on CD103 + T RM in both in vitro and murine PSC models. Our study suggests that targeting pathogenic CD103 + T RM with itaconate has therapeutic potential in PSC.
A Comparative Inflammation‐on‐a‐Chip with a Complete 3D Interface: Pharmacological Applications in COPD‐Induced Neutrophil Migration
Authors: Soohyun Kim, Sung Kyun Lee, Ahryeong Son, Jong‐Hwan Lee, Hong Gi Kim
Journal: Advanced Healthcare Materials (2023)

Chronic obstructive pulmonary disease (COPD) is a slow-progressing inflammatory lung disease that is associated with high mortality and disability. There is a lack of appropriate preclinical models of COPD, which hampers drug discovery efforts. Herein, a comparative inflammation-on-a-chip (IoC) is developed with a complete 3D interface without the formation of any micropillar and phaseguide structures that replicated chemoattractant-induced neutrophil transendothelial migration (NTEM), a key feature of COPD. The IoC model is used to evaluate the pharmacological effects of CXCR2 inhibitors (MK-7123, AZD5069, and SB225002) on the migration of neutrophil-like cells in the presence of plasma samples from patients with COPD. This is the first study to evaluate inhibitors of CXCR2-dependent NTEM in a comparative IoC model that mimics the physiological 3D microenvironment, consisting of an endothelial barrier, extracellular compartment, and inflammatory conditions. This IoC model will be useful to investigate COPD severity using patient samples, and will aid basic and translational research involving NTEM.
Ambient Air Pollution and Risk of Enterotomy, Gastrointestinal Cancer, and All-Cause Mortality among 4,708 Individuals with Inflammatory Bowel Disease: A Prospective Cohort Study
Authors: Jie Chen, Lintao Dan, Yuhao Sun, Shuai Yuan, Weilin Liu, Xuejie Chen, Fangyuan Jiang, Tian Fu, Han Zhang, Minzi Deng, Xiaoyan Wang, Xue Li
Journal: Environmental Health Perspectives (2023)

Background: Previous studies indicated that air pollution plausibly increases the risk of adverse outcomes in inflammatory bowel disease (IBD) via proinflammatory mechanisms. However, there is scant epidemiological data and insufficient prospective evidence assessing associations between ambient air pollution and clinical outcomes of IBD. Objectives: We aimed to investigate the associations between ambient air pollution and clinical outcomes among individuals with IBD. Methods: Leveraging data from the UK Biobank, we included 4,708 individuals with IBD recruited in the period 2006–2010 in this study. A land use regression model was used to assess annual mean concentrations of ambient air pollutants nitrogen including oxides (NOx), nitrogen dioxide (NO2), and particulate matter (PM) with aerodynamic diameter ≤10μm (PM10) and PM with aerodynamic diameter ≤2.5μm (PM2.5). Individuals with IBD were followed up for incident clinical outcomes of enterotomy, gastrointestinal cancer, and all-cause mortality, ascertained via death registry, inpatient, primary care, and cancer registry data. Cox proportional hazard model was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for the magnitude of the associations. Results: During a mean follow-up of 12.0 y, 265 enterotomy events, 124 incident gastrointestinal cancer, and 420 death events were documented among individuals with IBD. We found that each interquartile range (IQR) increase in exposure to PM2.5 was associated with increased risk of enterotomy (HR=1.16; 95% CI: 1.00, 1.34, p=0.043), whereas an IQR increase in exposure to NOx (HR=1.10; 95% CI: 1.01, 1.20, p=0.016), NO2 (HR=1.16; 95% CI: 1.03, 1.29, p=0.010), PM10 (HR=1.15; 95% CI: 1.03, 1.30, p=0.015), and PM2.5 (HR=1.14; 95% CI: 1.02, 1.28, p=0.019) was associated with increased risk of all-cause mortality among individuals with IBD. We did not observe any significant associations between air pollutants and gastrointestinal cancer in the primary analyses. Consistent results were observed in subgroup and sensitivity analyses. Conclusions: Ambient pollution exposure was associated with an increased risk of enterotomy and all-cause mortality among individuals with IBD, highlighting the important role of environmental health in improving the prognosis of IBD. https://doi.org/10.1289/EHP12215
Enhancement of the viability of T cells electroporated with DNA via osmotic dampening of the DNA-sensing cGAS–STING pathway
Authors: Jing An, Chuan-Ping Zhang, Hou-Yuan Qiu, Hong-Xia Zhang, Qiu-Bing Chen, Yu-Ming Zhang, Xin-Lin Lei, Cai-Xiang Zhang, Hao Yin, Ying Zhang
Journal: Nature Biomedical Engineering (2023)
Bi- and trispecific immune cell engagers for immunotherapy of hematological malignancies
Authors: Antonio Tapia-Galisteo, Luis Álvarez-Vallina, Laura Sanz
Journal: Journal of Hematology & Oncology (2023)

Abstract Immune cell engagers are engineered antibodies with at least one arm binding a tumor-associated antigen and at least another one directed against an activating receptor in immune effector cells: CD3 for recruitment of T cells and CD16a for NK cells. The first T cell engager (the anti-CD19 blinatumomab) was approved by the FDA in 2014, but no other one hit the market until 2022. Now the field is gaining momentum, with three approvals in 2022 and 2023 (as of May): the anti-CD20 × anti-CD3 mosunetuzumab and epcoritamab and the anti-B cell maturation antigen (BCMA) × anti-CD3 teclistamab, and another three molecules in regulatory review. T cell engagers will likely revolutionize the treatment of hematological malignancies in the short term, as they are considerably more potent than conventional monoclonal antibodies recognizing the same tumor antigens. The field is thriving, with a plethora of different formats and targets, and around 100 bispecific T cell engagers more are already in clinical trials. Bispecific NK cell engagers are also in early-stage clinical studies and may offer similar efficacy with milder side effects. Trispecific antibodies (engaging either T cell or NK cell receptors) raise the game even further with a third binding moiety, which allows either the targeting of an additional tumor-associated antigen to increase specificity and avoid immune escape or the targeting of additional costimulatory receptors on the immune cell to improve its effector functions. Altogether, these engineered molecules may change the paradigm of treatment for relapsed or refractory hematological malignancies.
High-grade glioma in infants and young children is histologically, molecularly, and clinically diverse: Results from the SJYC07 trial and institutional experience
Authors: Jason Chiang, Aditi Bagchi, Xiaoyu Li, Sandeep K Dhanda, Jie Huang, Soniya N Pinto, Edgar Sioson, James Dalton, Ruth G Tatevossian, Sujuan Jia, Sonia Partap, Paul G Fisher, Daniel C Bowers, Timothy E G Hassall, Congyu Lu, Airen Zaldivar-Peraza, Karen D Wright, Alberto Broniscer, Ibrahim Qaddoumi, Santhosh A Upadhyaya, Anna Vinitsky, Noah D Sabin, Brent A Orr, Paul Klimo, Frederick A Boop, Jason M Ashford, Heather M Conklin, Arzu Onar-Thomas, Xin Zhou, David W Ellison, Amar Gajjar, Giles W Robinson
Journal: Neuro-Oncology (2023)

High-grade gliomas (HGG) in young children pose a challenge due to favorable but unpredictable outcomes. While retrospective studies broadened our understanding of tumor biology, prospective data is lacking.